Abstract:This study explores the application of supervised and unsupervised autoencoders (AEs) to automate nuclei classification in clear cell renal cell carcinoma (ccRCC) images, a diagnostic task traditionally reliant on subjective visual grading by pathologists. We evaluate various AE architectures, including standard AEs, contractive AEs (CAEs), and discriminative AEs (DAEs), as well as a classifier-based discriminative AE (CDAE), optimized using the hyperparameter tuning tool Optuna. Bhattacharyya distance is selected from several metrics to assess class separability in the latent space, revealing challenges in distinguishing adjacent grades using unsupervised models. CDAE, integrating a supervised classifier branch, demonstrated superior performance in both latent space separation and classification accuracy. Given that CDAE-CNN achieved notable improvements in classification metrics, affirming the value of supervised learning for class-specific feature extraction, F1 score was incorporated into the tuning process to optimize classification performance. Results show significant improvements in identifying aggressive ccRCC grades by leveraging the classification capability of AE through latent clustering followed by fine-grained classification. Our model outperforms the current state of the art, CHR-Network, across all evaluated metrics. These findings suggest that integrating a classifier branch in AEs, combined with neural architecture search and contrastive learning, enhances grading automation in ccRCC pathology, particularly in detecting aggressive tumor grades, and may improve diagnostic accuracy.